SK285582B6 - Opticky aktívny derivát pyridyl-4H-1,2,4-oxadiazínu a jeho použitie na výrobu liečiva na liečenie vaskulárnych ochorení - Google Patents
Opticky aktívny derivát pyridyl-4H-1,2,4-oxadiazínu a jeho použitie na výrobu liečiva na liečenie vaskulárnych ochorení Download PDFInfo
- Publication number
- SK285582B6 SK285582B6 SK234-2001A SK2342001A SK285582B6 SK 285582 B6 SK285582 B6 SK 285582B6 SK 2342001 A SK2342001 A SK 2342001A SK 285582 B6 SK285582 B6 SK 285582B6
- Authority
- SK
- Slovakia
- Prior art keywords
- pyridyl
- oxadiazine
- piperidinyl
- dihydro
- methyl
- Prior art date
Links
- 239000003814 drug Substances 0.000 title claims description 10
- 208000019553 vascular disease Diseases 0.000 title claims description 8
- 238000004519 manufacturing process Methods 0.000 title claims description 5
- 239000004480 active ingredient Substances 0.000 claims abstract description 10
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 8
- QWVRTSZDKPRPDF-UHFFFAOYSA-N 5-(piperidin-1-ylmethyl)-3-pyridin-3-yl-5,6-dihydro-2h-1,2,4-oxadiazine Chemical compound C1CCCCN1CC(N=1)CONC=1C1=CC=CN=C1 QWVRTSZDKPRPDF-UHFFFAOYSA-N 0.000 claims description 27
- 150000003839 salts Chemical class 0.000 claims description 14
- 239000002253 acid Substances 0.000 claims description 10
- 201000010099 disease Diseases 0.000 claims description 7
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 7
- 206010019280 Heart failures Diseases 0.000 claims description 6
- 230000006496 vascular abnormality Effects 0.000 claims description 6
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 5
- 230000002265 prevention Effects 0.000 claims description 5
- 239000000969 carrier Substances 0.000 claims description 2
- 150000001875 compounds Chemical class 0.000 abstract description 23
- 125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 abstract description 5
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 18
- QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 14
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 12
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 8
- 239000000203 mixture Substances 0.000 description 7
- 239000000243 solution Substances 0.000 description 7
- 241000700159 Rattus Species 0.000 description 6
- 238000002474 experimental method Methods 0.000 description 6
- 238000000034 method Methods 0.000 description 6
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 5
- 208000028867 ischemia Diseases 0.000 description 5
- 238000002360 preparation method Methods 0.000 description 5
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 4
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 239000008187 granular material Substances 0.000 description 4
- 239000008101 lactose Substances 0.000 description 4
- 235000019359 magnesium stearate Nutrition 0.000 description 4
- 239000000463 material Substances 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- 230000004044 response Effects 0.000 description 4
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 3
- 206010061216 Infarction Diseases 0.000 description 3
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 210000000038 chest Anatomy 0.000 description 3
- 210000004351 coronary vessel Anatomy 0.000 description 3
- 239000008298 dragée Substances 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 230000008753 endothelial function Effects 0.000 description 3
- 238000004128 high performance liquid chromatography Methods 0.000 description 3
- 230000007574 infarction Effects 0.000 description 3
- 208000010125 myocardial infarction Diseases 0.000 description 3
- WEXRUCMBJFQVBZ-UHFFFAOYSA-N pentobarbital Chemical compound CCCC(C)C1(CC)C(=O)NC(=O)NC1=O WEXRUCMBJFQVBZ-UHFFFAOYSA-N 0.000 description 3
- 230000010412 perfusion Effects 0.000 description 3
- 230000001292 preischemic effect Effects 0.000 description 3
- 238000000746 purification Methods 0.000 description 3
- 229940076279 serotonin Drugs 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- 239000003826 tablet Substances 0.000 description 3
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 2
- 241000282412 Homo Species 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- 230000004071 biological effect Effects 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 230000036772 blood pressure Effects 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 230000006378 damage Effects 0.000 description 2
- 238000000354 decomposition reaction Methods 0.000 description 2
- 238000004090 dissolution Methods 0.000 description 2
- 230000002140 halogenating effect Effects 0.000 description 2
- ZFGMDIBRIDKWMY-PASTXAENSA-N heparin Chemical compound CC(O)=N[C@@H]1[C@@H](O)[C@H](O)[C@@H](COS(O)(=O)=O)O[C@@H]1O[C@@H]1[C@@H](C(O)=O)O[C@@H](O[C@H]2[C@@H]([C@@H](OS(O)(=O)=O)[C@@H](O[C@@H]3[C@@H](OC(O)[C@H](OS(O)(=O)=O)[C@H]3O)C(O)=O)O[C@@H]2O)CS(O)(=O)=O)[C@H](O)[C@H]1O ZFGMDIBRIDKWMY-PASTXAENSA-N 0.000 description 2
- 238000001802 infusion Methods 0.000 description 2
- 210000005246 left atrium Anatomy 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
- LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 2
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 2
- 239000008108 microcrystalline cellulose Substances 0.000 description 2
- 229940016286 microcrystalline cellulose Drugs 0.000 description 2
- 208000031225 myocardial ischemia Diseases 0.000 description 2
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 2
- 230000003287 optical effect Effects 0.000 description 2
- 210000003540 papillary muscle Anatomy 0.000 description 2
- 229960001412 pentobarbital Drugs 0.000 description 2
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 2
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 2
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 2
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 2
- 230000009090 positive inotropic effect Effects 0.000 description 2
- 229920001592 potato starch Polymers 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- 230000001681 protective effect Effects 0.000 description 2
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
- 230000010410 reperfusion Effects 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 230000004083 survival effect Effects 0.000 description 2
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 2
- -1 (-) - L-dibenzoyltartaric acid monohydrate Chemical class 0.000 description 1
- YONLFQNRGZXBBF-ZIAGYGMSSA-N (2r,3r)-2,3-dibenzoyloxybutanedioic acid Chemical compound O([C@@H](C(=O)O)[C@@H](OC(=O)C=1C=CC=CC=1)C(O)=O)C(=O)C1=CC=CC=C1 YONLFQNRGZXBBF-ZIAGYGMSSA-N 0.000 description 1
- HKGLOANNRIYNNS-BTJKTKAUSA-N (z)-but-2-enedioic acid;5-(piperidin-1-ylmethyl)-3-pyridin-3-yl-5,6-dihydro-2h-1,2,4-oxadiazine Chemical compound OC(=O)\C=C/C(O)=O.C1CCCCN1CC(N=1)CONC=1C1=CC=CN=C1 HKGLOANNRIYNNS-BTJKTKAUSA-N 0.000 description 1
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 1
- 238000005160 1H NMR spectroscopy Methods 0.000 description 1
- OCQAXYHNMWVLRH-UHFFFAOYSA-N 2,3-dibenzoyl-2,3-dihydroxybutanedioic acid Chemical class C=1C=CC=CC=1C(=O)C(O)(C(O)=O)C(O)(C(=O)O)C(=O)C1=CC=CC=C1 OCQAXYHNMWVLRH-UHFFFAOYSA-N 0.000 description 1
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 description 1
- AVKGCNAECFSXHH-UHFFFAOYSA-N 5-(piperidin-1-ylmethyl)-3-pyridin-3-yl-5,6-dihydro-2h-1,2,4-oxadiazine;hydrochloride Chemical compound Cl.C1CCCCN1CC(N=1)CONC=1C1=CC=CN=C1 AVKGCNAECFSXHH-UHFFFAOYSA-N 0.000 description 1
- KRDJXQILWJDTAQ-UHFFFAOYSA-N 5-(piperidin-1-ylmethyl)-3-pyridin-3-yl-5,6-dihydro-2h-1,2,4-oxadiazine;sulfuric acid Chemical compound OS(O)(=O)=O.C1CCCCN1CC(N=1)CONC=1C1=CC=CN=C1 KRDJXQILWJDTAQ-UHFFFAOYSA-N 0.000 description 1
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 1
- JHDYJJZPWVTMRM-UHFFFAOYSA-N Br.C1CCCCN1CC(N=1)CONC=1C1=CC=CN=C1 Chemical compound Br.C1CCCCN1CC(N=1)CONC=1C1=CC=CN=C1 JHDYJJZPWVTMRM-UHFFFAOYSA-N 0.000 description 1
- 208000024172 Cardiovascular disease Diseases 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- 206010065420 Coronary artery dilatation Diseases 0.000 description 1
- 206010011086 Coronary artery occlusion Diseases 0.000 description 1
- 101710088194 Dehydrogenase Proteins 0.000 description 1
- 206010020772 Hypertension Diseases 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
- 241000283984 Rodentia Species 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- 229910000831 Steel Inorganic materials 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 229910021417 amorphous silicon Inorganic materials 0.000 description 1
- 210000000709 aorta Anatomy 0.000 description 1
- 230000006793 arrhythmia Effects 0.000 description 1
- 206010003119 arrhythmia Diseases 0.000 description 1
- 210000001367 artery Anatomy 0.000 description 1
- 230000001746 atrial effect Effects 0.000 description 1
- 235000013871 bee wax Nutrition 0.000 description 1
- 239000012166 beeswax Substances 0.000 description 1
- UBAZGMLMVVQSCD-UHFFFAOYSA-N carbon dioxide;molecular oxygen Chemical compound O=O.O=C=O UBAZGMLMVVQSCD-UHFFFAOYSA-N 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 208000026106 cerebrovascular disease Diseases 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 229940110456 cocoa butter Drugs 0.000 description 1
- 235000019868 cocoa butter Nutrition 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- 239000002178 crystalline material Substances 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 230000003205 diastolic effect Effects 0.000 description 1
- 230000000916 dilatatory effect Effects 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- 238000006073 displacement reaction Methods 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 230000002526 effect on cardiovascular system Effects 0.000 description 1
- 230000003511 endothelial effect Effects 0.000 description 1
- 210000003038 endothelium Anatomy 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 230000007717 exclusion Effects 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 230000004907 flux Effects 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 239000007903 gelatin capsule Substances 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 230000000004 hemodynamic effect Effects 0.000 description 1
- 229920000669 heparin Polymers 0.000 description 1
- 229920003063 hydroxymethyl cellulose Polymers 0.000 description 1
- 229940031574 hydroxymethyl cellulose Drugs 0.000 description 1
- 230000001631 hypertensive effect Effects 0.000 description 1
- 238000010191 image analysis Methods 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 239000012442 inert solvent Substances 0.000 description 1
- 239000003978 infusion fluid Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 230000000297 inotrophic effect Effects 0.000 description 1
- 238000007689 inspection Methods 0.000 description 1
- 230000000302 ischemic effect Effects 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 239000004292 methyl p-hydroxybenzoate Substances 0.000 description 1
- 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
- 229960002216 methylparaben Drugs 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 125000000896 monocarboxylic acid group Chemical group 0.000 description 1
- 210000004165 myocardium Anatomy 0.000 description 1
- 230000001338 necrotic effect Effects 0.000 description 1
- 238000011587 new zealand white rabbit Methods 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 239000012044 organic layer Substances 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 229910052697 platinum Inorganic materials 0.000 description 1
- 239000002798 polar solvent Substances 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 230000036316 preload Effects 0.000 description 1
- 238000004080 punching Methods 0.000 description 1
- 238000011002 quantification Methods 0.000 description 1
- 230000003134 recirculating effect Effects 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 239000006215 rectal suppository Substances 0.000 description 1
- 229940100618 rectal suppository Drugs 0.000 description 1
- 230000001172 regenerating effect Effects 0.000 description 1
- 230000000284 resting effect Effects 0.000 description 1
- 210000005245 right atrium Anatomy 0.000 description 1
- 238000006798 ring closing metathesis reaction Methods 0.000 description 1
- CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 1
- 229940081974 saccharin Drugs 0.000 description 1
- 235000019204 saccharin Nutrition 0.000 description 1
- 239000000901 saccharin and its Na,K and Ca salt Substances 0.000 description 1
- 239000000523 sample Substances 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 230000035939 shock Effects 0.000 description 1
- 238000007873 sieving Methods 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000002594 sorbent Substances 0.000 description 1
- 238000011699 spontaneously hypertensive rat Methods 0.000 description 1
- 230000006641 stabilisation Effects 0.000 description 1
- 238000011105 stabilization Methods 0.000 description 1
- 229910001220 stainless steel Inorganic materials 0.000 description 1
- 239000010935 stainless steel Substances 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 239000010959 steel Substances 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- MUUHXGOJWVMBDY-UHFFFAOYSA-L tetrazolium blue Chemical compound [Cl-].[Cl-].COC1=CC(C=2C=C(OC)C(=CC=2)[N+]=2N(N=C(N=2)C=2C=CC=CC=2)C=2C=CC=CC=2)=CC=C1[N+]1=NC(C=2C=CC=CC=2)=NN1C1=CC=CC=C1 MUUHXGOJWVMBDY-UHFFFAOYSA-L 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
- 210000003556 vascular endothelial cell Anatomy 0.000 description 1
- 230000000304 vasodilatating effect Effects 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
- A61K31/5355—Non-condensed oxazines and containing further heterocyclic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/14—Vasoprotectives; Antihaemorrhoidals; Drugs for varicose therapy; Capillary stabilisers
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Cardiology (AREA)
- Medicinal Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Heart & Thoracic Surgery (AREA)
- Vascular Medicine (AREA)
- Hospice & Palliative Care (AREA)
- Urology & Nephrology (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| HU9802897A HU226617B1 (en) | 1998-12-14 | 1998-12-14 | Optically active pyridyl-4h-1,2,4-oxadiazine derivatives, and pharmaceutical composition containing the compound as active ingredient |
| PCT/HU1999/000095 WO2000035914A1 (en) | 1998-12-14 | 1999-12-07 | Optically active pyridyl-4h-1,2,4-oxadiazine derivative and its use in the treatment of vascular diseases |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| SK2342001A3 SK2342001A3 (en) | 2001-08-06 |
| SK285582B6 true SK285582B6 (sk) | 2007-04-05 |
Family
ID=10991166
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| SK234-2001A SK285582B6 (sk) | 1998-12-14 | 1999-12-07 | Opticky aktívny derivát pyridyl-4H-1,2,4-oxadiazínu a jeho použitie na výrobu liečiva na liečenie vaskulárnych ochorení |
Country Status (27)
| Country | Link |
|---|---|
| US (1) | US6384029B1 (cs) |
| EP (1) | EP1147105B1 (cs) |
| JP (2) | JP2002532498A (cs) |
| KR (1) | KR100661774B1 (cs) |
| AT (1) | ATE266027T1 (cs) |
| AU (1) | AU765336B2 (cs) |
| BG (1) | BG65179B1 (cs) |
| BR (1) | BR9913982A (cs) |
| CA (1) | CA2340734C (cs) |
| CZ (1) | CZ300764B6 (cs) |
| DE (1) | DE69917074T2 (cs) |
| DK (1) | DK1147105T3 (cs) |
| EE (1) | EE04551B1 (cs) |
| ES (1) | ES2219091T3 (cs) |
| HR (1) | HRP20010133B1 (cs) |
| HU (1) | HU226617B1 (cs) |
| IL (1) | IL141515A (cs) |
| NO (1) | NO317649B1 (cs) |
| PL (1) | PL196584B1 (cs) |
| PT (1) | PT1147105E (cs) |
| RS (1) | RS50129B (cs) |
| RU (1) | RU2222538C2 (cs) |
| SI (1) | SI1147105T1 (cs) |
| SK (1) | SK285582B6 (cs) |
| UA (1) | UA70340C2 (cs) |
| WO (1) | WO2000035914A1 (cs) |
| ZA (1) | ZA200101182B (cs) |
Families Citing this family (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7384936B2 (en) | 2002-01-11 | 2008-06-10 | Cytrx Corporation | Carboxamidine derivatives and their use in the treatment of vascular diseases |
| KR100678577B1 (ko) * | 2006-09-11 | 2007-02-06 | 조만규 | 가정용 분전함 |
| CN102123729B (zh) | 2008-06-26 | 2015-04-29 | 奥菲泽米有限公司 | Hsp70作为酶促活性调节物的应用 |
| JP2010150243A (ja) | 2008-11-18 | 2010-07-08 | Santen Pharmaceut Co Ltd | ピリジン−３−カルバルデヒドｏ−（ピペリジン−１−イル−プロピル）−オキシム誘導体を有効成分として含有する網脈絡膜変性疾患の治療剤 |
| DK2646044T3 (da) | 2010-11-30 | 2019-11-25 | Orphazyme As | Metoder til at øge den intracellulære aktivitet af Hsp70 |
| HUP1100534A2 (en) | 2011-09-26 | 2013-04-29 | Balazs Dr Hazay | Pharmaceutical composition for the treatment of muscle atrophy |
| KR102487452B1 (ko) | 2014-09-15 | 2023-01-10 | 오르파짐 에이/에스 | 아리모클로몰 제제 |
| US10898476B2 (en) | 2016-04-13 | 2021-01-26 | Orphazyme A/S | Heat shock proteins and cholesterol homeostasis |
| WO2017186919A1 (en) | 2016-04-29 | 2017-11-02 | Orphazyme Aps | Arimoclomol for treating glucocerebrosidase associated disorders |
| RU2019141123A (ru) | 2017-05-24 | 2021-06-24 | Орфазим А/С | Индукторы белков теплового шока и лобно-височные нарушения |
| AU2019276048B2 (en) | 2018-05-28 | 2025-09-04 | Zevra Denmark A/S | Hsp70 protein levels in PBMC samples as biomarker for disease |
| IL303026A (en) | 2020-11-19 | 2023-07-01 | Zevra Denmark As | Processes for preparing arimoclomol citrate and intermediates thereof |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AT395853B (de) * | 1991-01-31 | 1993-03-25 | Chem Pharm Forsch Gmbh | Neue imidazolderivate, verfahren zu ihrer herstellung und ihre verwendung |
| HU222994B1 (hu) * | 1995-11-02 | 2004-01-28 | BIOREX Kutató és Fejlesztő Rt. | Hidroxilaminszármazékok és azok alkalmazása sejtek molekuláris chaperon-termelésének fokozására alkalmas gyógyszerkészítmények előállítására |
| AU7324196A (en) * | 1995-11-03 | 1997-05-22 | Global Trading Uk Limited | Apparatus for dispensing and filling bags at a checkout counter of a supermarket |
| UA64716C2 (en) * | 1996-08-09 | 2004-03-15 | Pharmaceuticals for therapy or prevention of illnesses connected with dysfunction of vascular endothelial cells |
-
1998
- 1998-12-14 HU HU9802897A patent/HU226617B1/hu not_active IP Right Cessation
-
1999
- 1999-07-12 UA UA2001063850A patent/UA70340C2/uk unknown
- 1999-12-07 AU AU17906/00A patent/AU765336B2/en not_active Expired
- 1999-12-07 PT PT99961225T patent/PT1147105E/pt unknown
- 1999-12-07 DE DE69917074T patent/DE69917074T2/de not_active Expired - Lifetime
- 1999-12-07 JP JP2000588174A patent/JP2002532498A/ja not_active Withdrawn
- 1999-12-07 RS YUP-250/01A patent/RS50129B/sr unknown
- 1999-12-07 SK SK234-2001A patent/SK285582B6/sk not_active IP Right Cessation
- 1999-12-07 WO PCT/HU1999/000095 patent/WO2000035914A1/en not_active Ceased
- 1999-12-07 DK DK99961225T patent/DK1147105T3/da active
- 1999-12-07 BR BR9913982-0A patent/BR9913982A/pt not_active Application Discontinuation
- 1999-12-07 IL IL14151599A patent/IL141515A/xx not_active IP Right Cessation
- 1999-12-07 SI SI9930566T patent/SI1147105T1/xx unknown
- 1999-12-07 RU RU2001118854/04A patent/RU2222538C2/ru not_active IP Right Cessation
- 1999-12-07 ES ES99961225T patent/ES2219091T3/es not_active Expired - Lifetime
- 1999-12-07 CA CA002340734A patent/CA2340734C/en not_active Expired - Lifetime
- 1999-12-07 PL PL346767A patent/PL196584B1/pl not_active IP Right Cessation
- 1999-12-07 CZ CZ20011550A patent/CZ300764B6/cs not_active IP Right Cessation
- 1999-12-07 EP EP99961225A patent/EP1147105B1/en not_active Expired - Lifetime
- 1999-12-07 KR KR1020017002870A patent/KR100661774B1/ko not_active Expired - Fee Related
- 1999-12-07 EE EEP200100188A patent/EE04551B1/xx not_active IP Right Cessation
- 1999-12-07 AT AT99961225T patent/ATE266027T1/de active
- 1999-12-07 US US09/762,949 patent/US6384029B1/en not_active Expired - Lifetime
- 1999-12-07 HR HR20010133A patent/HRP20010133B1/xx not_active IP Right Cessation
-
2001
- 2001-02-12 ZA ZA200101182A patent/ZA200101182B/en unknown
- 2001-03-14 BG BG105342A patent/BG65179B1/bg unknown
- 2001-05-10 NO NO20012310A patent/NO317649B1/no not_active IP Right Cessation
-
2011
- 2011-06-08 JP JP2011128516A patent/JP5620340B2/ja not_active Expired - Lifetime
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP5620340B2 (ja) | 光学活性ピリジル−４ｈ−１，２，４−オキサジアジン誘導体およびその血管疾患の治療における使用 | |
| JP4316794B2 (ja) | イソキノリン誘導体及び医薬 | |
| JP2011201916A5 (cs) | ||
| JPWO1999020620A1 (ja) | イソキノリン誘導体及び医薬 | |
| JP5575979B2 (ja) | シアノ基を含有するチエノピリジンエステル誘導体、その調製方法、使用および組成物 | |
| EP0539153A1 (en) | Acridine derivative as therapeutic agent | |
| JPH05271208A (ja) | １，４‐ベンゾチアゼピン誘導体 | |
| US11130766B2 (en) | Deuterated thienopiperidine derivatives, manufacturing method, and application thereof | |
| AU621067B2 (en) | A cardioprotective agent and a therapeutic agent for ischemic disease comprising N-containing heterocyclic compounds, and a process for the preparation of the same compounds | |
| US5912261A (en) | Carboxyalkyl heterocyclic derivatives | |
| CN102603755B (zh) | 一类具有协同氟康唑抗耐药真菌作用的化合物 | |
| CN114349745B (zh) | 一种用于治疗心肌缺血的药物及其制备方法 | |
| JP3262800B2 (ja) | 療用複素環化合物 | |
| KR20030002304A (ko) | 3-페닐-3,7-디아자비시클로[3.3.1]노난 화합물들과 이들의제조방법 및 이러한 화합물들을 포함하는 약제들 | |
| CN118221649A (zh) | 氟取代的吲唑化合物的晶型及其用途 | |
| CN118221651A (zh) | 氟取代的吲唑化合物的晶型及其用途 | |
| JP2001114699A (ja) | キマーゼ阻害作用を有する化合物を有効成分とする血管新生阻害剤 | |
| WO2004011433A1 (en) | Organic acid salt of amlodipine | |
| HUP0500684A2 (en) | Use of 5-chloro-4-[3-[n-[2-(3,4-dimethoxyphenyl-ethyl)]-n-methylamino]-propylamino]-3-(2h)pyridazinone as acetylcholine dependent potassium channel inhibitor |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MM4A | Patent lapsed due to non-payment of maintenance fees |
Effective date: 20111207 |